Abstract: SA-OR83
Risk Factors and Impact of Peritoneal Podoplanin in Children on Chronic Peritoneal Dialysis
Session Information
- Pediatric Nephrology: Clinical and Genetic Studies
November 04, 2023 | Location: Room 105, Pennsylvania Convention Center
Abstract Time: 05:15 PM - 05:24 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Bartosova, Maria, UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
- Zhang, Conghui, UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
- Eibensteiner, Fabian, Medizinische Universitat Wien, Wien, Austria
- Herzog, Rebecca, Medizinische Universitat Wien, Wien, Austria
- Marinovic, Iva, UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
- Schaefer, Betti, UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
- Vondrak, Karel, University Hospital Motol Prague, Prague, Czechia
- Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States
- Kratochwill, Klaus, Medizinische Universitat Wien, Wien, Austria
- Schmitt, Claus Peter, UniversitatsKlinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany
Group or Team Name
- Int. Pediatric PD Biopsy Study Group.
Background
Diffuse, peritoneal podoplanin staining (DPS) positivity has been described with encapsulating peritoneal sclerosis (EPS) in patients on peritoneal dialysis (PD). The pathophysiological role in PD is uncertain.
Methods
Peritoneal tissues from 250 children (8.5, IQR 2.5, 13.2 years), with normal renal function (NRF), CKD5, and on chronic PD with fluids that contain low and high glucose degradation product (GDP) concentrations underwent digital histomorphometry and high-dimensional multiplexed imaging mass cytometry followed by deep learning-based segmentation and spatial single-cell and cellular neighbourhood interaction analysis.
Results
Children with NRF and CKD5 exhibited no DPS. 21% of children on low-GDP PD and 46% on high-GDP PD were DPS positive, but without clinical, radiological or histological features of EPS. PD duration and peritonitis incidence were similar in DPS positive and as in non-DPS PD patients. DPS positive patients were younger, had higher dialytic glucose exposure and more arteriolar lumen narrowing. Dialytic glucose exposure, PD duration, lower body surface area (BSA) and epithelial-to-mesenchymal (EMT) transformed cell counts were independently associated with DPS. DPS and lower mesothelial surface coverage independently associated with arteriolopathy.
In subgroups matched for age, PD duration and dialytic glucose exposure, DPS positive children had higher submesothelial leucocyte (CD45+) and macrophage (CD68+) counts, and higher lipopolysaccharide and hyaluronan receptor CD44 abundance. DPS intensity was higher with history of peritonitis. Hierarchical clustering demonstrated highest similarity of DPS positive areas with CD68 positive areas, classified as M2 macrophages (CD68+CD163+), followed by fibroblastic cells (αSMA+PROX1-CD31-CD68-CD163-); DPS signals from M1 macrophages (CD68+CD163-) were low.
Conclusion
DPS is prevalent in children on PD devoid of EPS, and is independently associated with peritoneal arteriolopathy. Independent DPS risk factors are high dialytic glucose and GDP exposure, history of peritonitis, BSA, peritoneal inflammatory and EMT cell invasion; M2 macrophages presumably play a key role.
Funding
- Government Support – Non-U.S.